In the field of clinical examination, an immunoassay that utilizes an antigen-antibody reaction has been widely used to quantitatively determine a trace substance in the sample. In particular, latex immunoturbidimetric method that utilizes latex particles that support an antibody or the like (hereinafter may be referred to as “sensitized latex particles”) has been widely used in clinical laboratories and the like since the operation is easy, and only a short measurement time is required. When using latex immunoturbidimetric method, an antigen or an antibody in the sample is quantitatively determined by optically detecting a change in absorbance due to agglutination of the sensitized latex particles caused by formation of an immune complex between the antigen and the antibody. Such a change in absorbance is based on an apparent change in particle size due to agglutination of the sensitized latex particles.
Polystyrene-based latex particles that include polystyrene as the main component have been used for latex immunoturbidimetry since the polystyrene-based latex particles allow easy immobilization of an antigen or an antibody that specifically reacts with the detection target substance (in other words, it is easy to sensitize the latex particles), are relatively inexpensive, and allow easily control of a polymerization reaction (see Patent Document 1). However, the latex particles that include polystyrene as the main component, which have an advantage in that an antigen or an antibody can be physically adsorbed on the latex particles (in other words, the latex particles can be sensitized through physical adsorption) may cause agglutination of the sensitized latex particles that is not based on a specific reaction due to an antigen-antibody reaction, (i.e., non-specific reaction) due to their property of allowing non-detection target proteins or the like in the sample adsorbed thereon. Therefore, it has been desired to suppress such a non-specific reaction.
A technique has been known that blocks the latex particles sensitized with an antigen or an antibody with bovine serum albumin (BSA) or the like in order to suppress a non-specific reaction. However, a non-specific reaction may not be sufficiently suppressed by such a technique, and a high background value may be obtained. Therefore, suppression of a non-specific reaction has been a major challenge in preparing a reagent that can implement a high-sensitivity assay.
In Patent Document 2, a nonionic surfactant is added to the blocking buffer when sensitizing the latex particles with an antigen or an antibody, and a nonionic surfactant is added to the assay reagent in order to suppress a non-specific reaction. However, since the nonionic surfactant is present on the surface of the particles, and is also included in the assay reagent, a decrease in sensitivity may occur due to inhibition of an immune reaction, for example. Therefore, development of a method that suppresses a non-specific reaction by improving the latex particles has been desired.
Patent Document 3 discloses latex particles produced by emulsion polymerization that utilizes a nonionic surfactant or an anionic surfactant as an emulsifier, which the latex particles per se are designed to suppress a non-specific reaction, and can be easily produced. However, since the emulsifier is used at a concentration of 0.05 wt % or more based on the aqueous medium when producing the latex particles of Patent Document 3, a sufficient sensitivity may not be achieved using the obtained latex particles due to the effects of the residual emulsifier.